Adcy10-KO Mouse

Adcy10, also known as soluble adenylyl cyclase (sAC), is an enzyme involved in intracellular signaling. It is crucial for generating 3'⁻5'-cyclic adenosine monophosphate (cAMP), and its intracellular localization allows for the formation of unique cAMP microdomains controlling various physiological and pathological processes [2]. It is associated with pathways like the ADCY/PKA/HBP/YAP axis [1], and plays a significant role in multiple biological functions, such as sperm motility regulation, kidney stone-related processes, and brown adipose tissue thermogenesis.

In lung adenocarcinoma, endogenous glutamate accumulation can determine ferroptosis sensitivity by suppressing YAP via Adcy10-dependent mechanisms. Adcy10 acts as a key downstream target and diversifies the effects of glutamate on the PKA-dependent suppression of GFPT1 [1]. In the context of male fertility, proper Adcy10 (sAC) activity and a constant supply of cAMP are crucial for sperm motility regulation. A 2-bp deletion in Adcy10 coding region led to severe recessive asthenozoospermia in patients, and treatment with a cAMP analogue increased sperm motility, indicating the pathogenic role of the variant [3]. Also, in brown adipose tissue, Adcy10, as a CO2/bicarbonate sensor, mediates the effect of IDH on complex I activity through cAMP-EPAC1 signaling, maintaining the mitochondrial membrane potential and enabling thermogenesis [4].

In conclusion, Adcy10 is essential for various biological functions including sperm motility, ferroptosis sensitivity in lung adenocarcinoma, and brown adipose tissue thermogenesis. Gene-knockout or related functional studies in models like mice have been valuable in revealing its role in these processes, which has implications for understanding and potentially treating diseases such as asthenozoospermia and advanced-stage lung adenocarcinoma [1,3,4].